Recent studies from this and other laboratories have demonstrated that in addition to its enhancing and permissive in vitro effects, 2-mercaptoethanol (2-ME) is capable of activating murine lymphocytes to proliferation, to polyclonal antibody synthesis, and to polyclonal cytotoxicity. This compound appears to represent a different class of stimulant than the classical mitogens because it is orders of magnitude smaller in molecular weight and may well act at a point internal to the cell membrane. Therefore, experiments have been designed to study this activation process from a number of different directions. The state of maturity necessary before a population of cells becomes responsive to 2-ME will be determined. The relationship between cellular maturity and acquisition of functional capacity will be investigated with regard to polyclonal antibody production as induced by an array of mitogenic substances (including 2-ME). Using the sequential development of responsiveness to different mitogens as a time scale, the stage at which the B cell maturation block of CBA/N mice occurs will be assessed and placed in the perspective of this scale. Moreover, the role of acquisition of cell surface IgD in the generation of the response to 2-ME will be determined. Studies have been planned to probe the manner in which cells collaborate in order to amplify their response to non-specific activation. The experiments are designed to identify the B cell, T cell, or macrophage nature of the stimulator cell and the stimulator cell and the responding cell, as well as the role of identity at various histocompatibility loci in the interaction between these two cells. Attempts will be made to isolate and characterize the molecular entity mediating this cellular interaction and to localization subcellular site of action. The final objective of these studies is to identify and characterize the molecular species with which 2-ME interacts to trigger the cell. Attempts will be made to localize the 2-ME interaction site as to the organelle, class of molecule, and if possible, the particular molecule involved.